Project Summary Maternal effects comprise non-genetic influences on offspring phenotype resulting from the environmental experience of the mother. Prenatal stress is an important source of maternal effects, which can have profound effects on the resulting phenotype of the offspring, and, in humans, can lead to impaired growth, disruption of cognitive and emotional development, and physical disorders. Stress results in the secretion of stress hormones (i.e., glucocorticoids) that, although beneficial in the short-term, can lead to deterioration in the health of an individual if they remain chronically elevated. The particular focus in our proposed studies will be the prenatal maternal stress that ensues when immune responses of females are experimentally activated independently of the potentially confounding effects of infection during reproduction. Our proposed research employs a wild bird model that provides an excellent alternative model to evaluate maternal effects of prenatal stress because: (i) the endocrine systems of birds are similar to those of mammals, (ii) bird embryos are readily amenable to experimental manipulation within eggs, and (iii) wild birds are easily captured and manipulated in their natural environment, allowing inferences about the role of maternal stress to be made in a realistic evolutionary context. Our current expiring NIH-AREA project has revealed that experimentally induced immune responses lead to increased corticosterone levels in females and their eggs, and that this results in a significant influence on offspring size, health state, and immunity. We propose to build on this empirical foundation by: (i) characterizing the persistent influence of these maternal effects on the adult offspring phenotype, with specific reference to the hypothalamic-pituitary-adrenal (HPA) axis, parental competence, and sex-specific trans- generational effects; and (ii) evaluating directly the role of the primary avian glucocorticoid, corticosterone, in mediating these effects by: a) employing a noninvasive method of increasing maternal corticosterone in the absence of any overt prenatal stress and b) experimentally blocking or reducing circulating maternal corticosterone in immunostimulated females. The proposed research will meet a primary goal of the AREA (R15) program in that it will expose undergraduate students to research that combines both field and laboratory work in a hypothetico-deductive framework to address important biomedical questions in a natural setting.